Objective: To measure respiratory motion of the thoracic wall region in dogs using a real-time motion tracking system and compare the amount of respiratory motion between dogs positioned with and without a vacuum-formable cushion. Animals: 8 healthy adult mixed-breed dogs (median weight, 23 kg). Procedures: Dogs were anesthetized and positioned in sternal and dorsal recumbency with and without a vacuum-formable cushion. Three-dimensional movement of anatomic landmarks was measured with a real-time motion capture system that tracked the locations of infrared light–emitting diodes attached externally to the dorsal or ventral and lateral aspects of the thoracic wall. Results: Dogs positioned in sternal recumbency had significantly less cranial-to-caudal and left-to-right respiratory motion at the lateral aspect of the thoracic wall, compared with dogs positioned in dorsal recumbency, whether or not a cushion was used. For dogs treated in sternal recumbency, use of a cushion significantly increased the peak displacement vector (overall movement in 3-D space) for 3 of 4 marker locations on the dorsal thoracic wall. As respiratory rate increased, respiratory motion at the lateral and ventral aspects of the thoracic wall decreased when data for all dogs in dorsal recumbency were evaluated together. Conclusions and Clinical Relevance: Associations between respiratory rate and respiratory motion suggested that the use of rapid, shallow ventilation may be beneficial for dogs undergoing highly conformal radiation treatment. These results provide a basis for further research on respiratory motion in anesthetized dogs.

Objective: To investigate the effects of bevacizumab, a human monoclonal antibody against vascular endothelial growth factor, on the angiogenesis and growth of canine osteosarcoma cells xenografted in mice. Animals: 27 athymic nude mice. Procedures: To each mouse, highly metastasizing parent osteosarcoma cells of canine origin were injected into the left gastrocnemius muscle. Each mouse was then randomly allocated to 1 of 3 treatment groups: high-dose bevacizumab (4 mg/kg, IP), low-dose bevacizumab (2 mg/kg, IP), or control (no treatment). Tumor growth (the number of days required for the tumor to grow from 8 to 13 mm), vasculature, histomorphology, necrosis, and pulmonary metastasis were evaluated. Results: Mice in the high-dose bevacizumab group had significantly delayed tumor growth (mean ± SD, 13.4 ± 3.8 days; range, 9 to 21 days), compared with that for mice in the low-dose bevacizumab group (mean ± SD, 9.4 ± 1.5 days; range, 7 to 11 days) or control group (mean ± SD, 7. 2 ± 1.5 days; range, 4 to 9 days). Mice in the low-dose bevacizumab group also had significantly delayed tumor growth, compared with that for mice in the control group. Conclusions and Clinical Relevance: Results indicated that bevacizumab inhibited growth of canine osteosarcoma cells xenografted in mice, which suggested that vascular endothelial growth factor inhibitors may be clinically useful for the treatment of osteosarcoma in dogs. Impact for Human Medicine: Canine osteosarcoma is used as a research model for human osteosarcoma; therefore, bevacizumab may be clinically beneficial for the treatment of osteosarcoma in humans.

Objective: To compare navicular bone marrow lesion (BML) conspicuity in the feet of horses as determined via 2 fat-suppressed MRI techniques, including standard short tau inversion recovery (STIR) and inversion recovery gradient echo (IRGE). Sample: Feet (n = 150) of horses with lameness referable to the distal portion of the digit. Procedures: STIR and IRGE sequences were obtained prospectively in all feet with a standing low-field equine MRI system. Presence of a BML was ascertained by identification of a characteristic combination of marrow alterations in T1-weighted, T2*-weighted, T2-weighted, and STIR images. Signal-to-noise and contrast-to-noise ratios were calculated on STIR and IRGE sequences in 56 feet with a navicular BML. Results: Signal-to-noise and contrast-to-noise ratios of both sequences correlated linearly (r = 0.87 and r = 0.92, respectively) but were significantly higher for STIR images (mean ± SD, 22.6 ± 12.7 and 12.4 ± 11.4, respectively), compared with IRGE images (13.7 ± 8.0 and 5.9 ± 7.2, respectively). Conclusions and Clinical Relevance: Results suggested that the IRGE sequence revealed BMLs significantly less conspicuously, compared with the standard STIR sequence. The 2 techniques cannot be used interchangeably, and IRGE is therefore not recommended as the sole fat-suppressed sequence for routine equine standing MRI protocols.

Objective: To establish an in vivo method for matrix metalloproteinase (MMP)-2 and MMP-9 induction in horses via IV administration of lipopolysaccharide (LPS) and to evaluate the ability of doxycycline, oxytetracycline, flunixin meglumine, and pentoxifylline to inhibit equine MMP-2 and MMP-9 production. Animals: 29 adult horses of various ages and breeds and either sex. Procedures: In part 1, horses received an IV administration of LPS (n = 5) or saline (0.9% NaCl) solution (5). Venous blood samples were collected before and at specified times for 24 hours after infusion. Plasma was harvested and analyzed for MMP-2 and MMP-9 activities via zymography. In part 2, horses received doxycycline (n = 5), oxytetracycline (5), flunixin meglumine (5), or pentoxifylline (4) before and for up to 12 hours after administration of LPS. Plasma was obtained and analyzed, and results were compared with results from the LPS-infused horses of part 1. Results: Administration of LPS significantly increased MMP-2 and MMP-9 activities in the venous circulation of horses. All MMP inhibitors significantly decreased LPS-induced increases in MMP activities but to differing degrees. Pentoxifylline and oxytetracycline appeared to be the most effective MMP-2 and MMP-9 inhibitors, whereas doxycycline and flunixin meglumine were more effective at inhibiting MMP-2 activity than MMP-9 activity. Conclusions and Clinical Relevance: IV administration of LPS to horses caused increased venous plasma activities of MMP-2 and MMP-9. These MMP activities were reduced by pentoxifylline and oxytetracycline, suggesting that further evaluation of these medications for treatment and prevention of MMP-associated diseases in horses is indicated.

The current study tested the benefit of commercially available spray-dried bovine colostrum (The Saskatoon Colostrum Company, Saskatoon, Saskatchewan) in raising snatch-farrowed, porcine-colostrum-deprived (SF-pCD) pigs. In experiment 1, 12 SF-pCD pigs received a liquid diet composed mainly of bovine colostrum from birth to day 10; 6 remained on the same liquid diet (COL), and the other 6 were fed a diet composed mainly of milk replacer (RPL) until weaning. In experiment 2, 12 SF-pCD pigs were fed mainly bovine colostrum before weaning; after weaning, 6 were fed a starter diet containing 20% (w/w) bovine colostrum powder (STARTER-COL), and the other 6 were fed a starter diet without any bovine colostrum (STARTER-CTRL) until termination (day 42 or day 49). In experiment 1 the COL pigs had significantly fewer fever-days than did the RPL pigs. In experiment 2 diarrhea, typhlocolitis, and pancreatic degeneration developed in 4 of the STARTER-COL pigs after weaning. In both experiments all the pigs fed mainly bovine colostrum before weaning survived until termination. All pigs tested free of swine influenza virus H1N1 and H3N2, Porcine reproductive and respiratory syndrome virus, and Porcine parvovirus. In experiment 2 all the pigs tested free of Porcine circovirus type 2 (PCV2), but some in both groups tested positive for Torque teno virus genogroups 1 and 2. In conclusion, with the use of snatch-farrowing and bovine colostrum, pigs can be raised in the absence of porcine maternal antibodies with 100% survival and freedom from most porcine pathogens of biologic relevance. This model is potentially suitable for animal disease research.

Objective: To evaluate the thermal antinociceptive effects and duration of action of nalbuphine decanoate after IM administration to Hispaniolan Amazon parrots (Amazona ventralis). Animals: 10 healthy adult Hispaniolan Amazon parrots of unknown sex. Procedures: Nalbuphine decanoate (33.7 mg/kg) or saline (0.9% NaCl) solution was administered IM in a randomized complete crossover experimental design (periods 1 and 2). Foot withdrawal threshold to a noxious thermal stimulus was used to evaluate responses. Baseline thermal withdrawal threshold was recorded 1 hour before drug or saline solution administration, and thermal foot withdrawal threshold measurements were repeated 1, 2, 3, 6, 12, 24, 48, and 72 hours after drug administration. Results: Nalbuphine decanoate administered IM at a dose of 33.7 mg/kg significantly increased thermal foot withdrawal threshold, compared with results after administration of saline solution during period 2, and also caused a significant change in withdrawal threshold for up to 12 hours, compared with baseline values. Conclusions and Clinical Relevance: Nalbuphine decanoate increased the foot withdrawal threshold to a noxious thermal stimulus in Hispaniolan Amazon parrots for up to 12 hours and provided a longer duration of action than has been reported for other nalbuphine formulations. Further studies with other types of nociceptive stimulation, dosages, and dosing intervals as well as clinical trials are needed to fully evaluate the analgesic effects of nalbuphine decanoate in psittacine birds.

Objective: To use microarray analysis to identify genes that are differentially expressed in horses with experimentally induced osteoarthritis. Animals: 24 horses. Procedures: During arthroscopic surgery, a fragment was created in the distal aspect of the radiocarpal bone in 1 forelimb of each horse to induce osteoarthritis. At day 14 after osteoarthritis induction, horses began exercise on a treadmill. Blood and synovial fluid samples were collected before and after surgery. At day 70, horses were euthanized and tissues were harvested for RNA analysis. An equine-specific microarray was used to measure RNA expression in peripheral WBCs. These data were compared with mRNA expression (determined via PCR assay) in WBCs, cartilage, and synovium as well as 2 protein biomarkers of cartilage matrix turnover in serum and synovial fluid. Results: A metalloproteinase domain-like protein decysin-1 (ADAMDEC1), glucose-regulated protein (GRP) 94, hematopoietic cell signal transducer (HCST), Unc-93 homolog A (hUNC-93A), and ribonucleotide reductase M2 polypeptide (RRM2) were significantly differentially regulated in WBCs of horses with osteoarthritis, compared with values prior to induction of osteoarthritis. There was correlation between the gene expression profile in WBCs, cartilage, and synovium and the cartilage turnover proteins. Gene expression of ADAMDEC1, hUNC-93A, and RRM2 in WBCs were correlated when measured via microarray analysis and PCR assay. Conclusions and Clinical Relevance: Expression of ADAMDEC1, GRP94, HCST, hUNC-93A, and RRM2 was differentially regulated in peripheral WBCs obtained from horses with experimentally induced osteoarthritis. Gene expression of ADAMDEC1, hUNC-93A, and RRM2 in peripheral WBCs has the potential for use as a diagnostic aid for osteoarthritis in horses.

Septic synovitis is a potentially debilitating and life-threatening disorder in horses. We hypothesized that a universal bacterial real-time PCR (RT-PCR) assay would have improved sensitivity and decreased turn-around time for detection of bacteria in synovial fluid (SF) samples. Forty-eight SF samples were collected from 36 horses that presented to two referral institutions with suspected septic synovitis. Universal RT-PCR, bacterial culture and SF analysis were performed on all samples, and an interpretation on the sample being septic or not was derived by three board certified specialists from the history, clinical assessment and SF characteristics. RT-PCR results were compared to a composite standard comprised of positive culture and interpretation by all three specialists of samples as “septic”. For 41 of 48 samples (85%), culture and RT-PCR results were concordant. Compared to the composite standard, 83% of samples were correctly classified by RT-PCR (turn-around time of approximately 4 hours). Relative sensitivity and specificity of RT-PCR were 87% and 72% respectively, and 56% and 86% for culture. Hence, universal RT-PCR was a rapid and highly sensitive test, which may accelerate diagnosis and improve outcome for horses with septic synovitis.

Objective-To measure concentrations of glutamate, aspartate, γ-aminobutyric acid (GABA), and glycine in CSF of dogs with experimentally induced subarachnoid hemorrhage (SAH) and to assess effects of cyclosporine and simvastatin on these concentrations. Sample-CSF samples from 13 dogs. Procedures-In a previous study, SAH was induced in dogs via 2 injections of autologous blood into the cerebellomedullary cistern 24 hours apart. Dogs were untreated (control; n = 5) or received simvastatin alone (4) or simvastatin in combination with cyclosporine (4). Samples of CSF were collected before the first blood injection (baseline; time 0), before the second blood injection, and on days 3, 7, and 10. For the study reported here, neurotransmitter concentrations in CSF were analyzed via high-performance liquid chromatography. Data were analyzed with a repeated-measures model with adjustments for multiple comparisons by use of the Tukey method. Results-In control dogs, the glutamate concentration peaked on day 3 and there was a significant increase in GABA and glutamate concentrations. Glutamate concentrations were significantly lower and glycine concentrations significantly higher on day 3 after administration of simvastatin alone or simvastatin in combination with cyclosporine, compared with concentrations for the control group. No significant differences in GABA and aspartate concentrations were detected among treatment groups at any time point. Conclusions and Clinical Relevance-Glutamate concentrations were increased in the CSF of dogs with SAH. Simvastatin administration attenuated high glutamate concentrations. A combination of immunosuppression and upregulation of nitric oxide synthase may be useful in lowering high glutamate concentrations in ischemic CNS conditions.

Objective—To determine the microvascular anatomy of the suspensory ligament of the forelimb of horses. Sample—17 cadaveric forelimbs from 9 adult horses with no known history of forelimb lameness. Procedures—The median artery of the forelimb was cannulated proximal to the antebrachiocarpal joint and injected with contrast medium for CT evaluation of the gross vasculature (n = 2) or India ink to evaluate the microvasculature (12). Routine histologic evaluation was performed on an additional 3 forelimbs to confirm the microvascular anatomy. Results—The vascular supply of the suspensory ligament of the forelimb originated from branches of the medial and lateral palmar and palmar metacarpal vessels as well as the proximal and distal deep palmar arches. An abundant, longitudinally oriented microvascular supply was evident throughout the length of the suspensory ligament without distinct variation among the proximal, midbody, and distal regions. The intraligamentous blood supply originated from a periligamentous vascular plexus that surrounded the suspensory ligament throughout its length. Histologic findings indicated the presence of a periligamentous connective tissue plexus, which contained vessels that penetrated and anastomosed with an extensive network of intraligamentous vessels throughout the length of the suspensory ligament. Conclusions and Clinical Relevance—The suspensory ligament of the equine forelimb had an abundant intraligamentous microvascular supply throughout its entire length. The absence of an obvious hypovascular area suggested that regional variations in healing rates of the suspensory ligament are not associated with the microvascular anatomy.